A Systematic Review and Meta-Analysis of Ayurvedic Herbal Preparations for Hypercholesterolemia.

Background and Objectives: Cardiovascular disease (CVD) is the leading cause of death globally and hypercholesterolemia is one of the major risk factors associated with CVD. Due to a growing body of research on side effects and long-term impacts of conventional CVD treatments, focus is shifting towards exploring alternative treatment approaches such as Ayurveda. However, because of a lack of strong scientific evidence, the safety and efficacy profiles of such interventions have not been well established. The current study aims to conduct a systematic review and meta-analyses to explore the strength of evidence on efficacy and safety of Ayurvedic herbs for hypercholesterolemia. Methods: Literature searches were conducted using databases including Medline, Cochrane Database, AMED, Embase, AYUSH research portal, and many others. All randomized controlled trials on individuals with hypercholesterolemia using Ayurvedic herbs (alone or in combination) with an exposure period of ≥ 3 weeks were included, with primary outcomes being total cholesterol levels, adverse events, and other cardiovascular events. The search strategy was determined with the help of the Cochrane Metabolic and Endocrine Disorders Group. Two researchers assessed the risk of each study individually and discrepancies were resolved by consensus or consultation with a third researcher. Meta-analysis was conducted using the inverse variance method and results are presented as forest plots and data summary tables using Revman v5.3. Results: A systematic review of 32 studies with 1386 participants found randomized controlled trials of three Ayurvedic herbs, Allium sativum (garlic), Commiphora mukul (guggulu), and Nigella sativa (black cumin) on hypercholesterolemia that met inclusion criteria. The average duration of intervention was 12 weeks. Meta-analysis of the trials showed that guggulu reduced total cholesterol and low-density lipoprotein levels by 16.78 mg/dL (95% C.I. 13.96 to 2.61; p-value = 0.02) and 18.78 mg/dL (95% C.I. 34.07 to 3.48; p = 0.02), respectively. Garlic reduced LDL-C by 10.37 mg/dL (95% C.I. -17.58 to -3.16; p-value = 0.005). Black cumin lowered total cholesterol by 9.28 mg/dL (95% C.I. -17.36, to -1.19, p-value = 0.02). Reported adverse side effects were minimal. Conclusion: There is moderate to high level of evidence from randomized controlled trials that the Ayurvedic herbs guggulu, garlic, and black cumin are moderately effective for reducing hypercholesterolemia. In addition, minimal evidence was found for any side effects associated with these herbs, positioning them as safe adjuvants to conventional treatments.

Lamotrigine add-on therapy for drug-resistant focal epilepsy.

BACKGROUND: This is an updated version of the Cochrane Review previously published in 2016. Epilepsy is a common neurological disorder, affecting 0.5% to 1% of the population. For nearly 30% of these people, their epilepsy is resistant to currently available drugs. Pharmacological treatment remains the first choice to control epilepsy. Lamotrigine is one of the newer antiepileptic drugs. Lamotrigine, in combination with other antiepileptic drugs (add-on), can reduce seizures, but with some adverse effects. OBJECTIVES: To determine the effects of lamotrigine on (1) seizures, (2) adverse-effect profile, and (3) cognition and quality of life, compared to placebo, when used as an add-on treatment for people with drug-resistant focal epilepsy. SEARCH METHODS: For the latest update of the review, we searched the following databases on 9 March 2020: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to March 06, 2020). CRS Web includes randomized or quasi-randomized, controlled trials from PubMed, EMBASE, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups including Epilepsy. No language restrictions were imposed. SELECTION CRITERIA: Randomised placebo-controlled trials of people with drug-resistant focal epilepsy of any age, in which an adequate method of concealment of randomisation was used. The studies were double-, single- or unblinded, placebo-controlled. For cross-over studies, the first treatment period was treated as a parallel trial. Eligible participants were adults or children with drug-resistant focal epilepsy. DATA COLLECTION AND ANALYSIS: For this update, two review authors independently assessed the trials for inclusion, and extracted data. Outcomes included 50% or greater reduction in seizure frequency, treatment withdrawal (any reason), adverse effects, effects on cognition and quality of life. Primary analyses were by intention-to-treat. Sensitivity best- and worse-case analyses were undertaken to account for missing outcome data. Pooled risk ratios (RRs) with 95% confidence intervals (95% Cls) were estimated for the primary outcomes of seizure frequency and treatment withdrawal. For adverse effects, we calculated pooled RRs and 99% Cls. MAIN RESULTS: We did not identify any new studies for this update, therefore, the results and conclusions are unchanged. In previous updates of this review, the authors found five parallel add-on studies, eight cross-over studies in adults or children with drug-resistant focal epilepsy, and one parallel add-on study with a responder-enriched design in infants. In total, these 14 studies included 1806 eligible participants (38 infants, 199 children, 1569 adults). Baseline phases ranged from four to 12 weeks; treatment phases from eight to 36 weeks. Overall, 11 studies (1243 participants) were rated as having low risk of bias, and three (697 participants) had unclear risk of bias due to lack of reported information around study design. Effective blinding of studies was reported in four studies (563 participants). The overall risk ratio (RR) for 50% or greater reduction in seizure frequency was 1.80 (95% CI 1.45 to 2.23; 12 trials, 1322 participants (adults and children); moderate-certainty evidence) indicating that lamotrigine was significantly more effective than placebo in reducing seizure frequency. The overall RR for treatment withdrawal (for any reason) was 1.11 (95% CI 0.91 to 1.37; 14 trials; 1806 participants; moderate-certainty evidence). The adverse events significantly associated with lamotrigine were: ataxia, dizziness, diplopia (double vision), and nausea. The RR of these adverse effects were as follows: ataxia 3.34 (99% Cl 2.01 to 5.55; 12 trials; 1525 participants; high-certainty evidence); dizziness 2.00 (99% Cl 1.52 to 2.64;13 trials; 1768 participants; moderate-certainty evidence); diplopia 3.79 (99% Cl 2.15 to 6.68; 3 trials, 944 participants; high-certainty evidence); nausea 1.81 (99% Cl 1.22 to 2.68; 12 studies,1486 participants; moderate-certainty evidence). The limited data available precluded any conclusions about effects on cognition and quality of life. No important heterogeneity between studies was found for any of the outcomes. Overall, we assessed the evidence as high to moderate certainty, due to incomplete data for some outcomes. AUTHORS' CONCLUSIONS: Lamotrigine as an add-on treatment for drug-resistant focal seizures appears to be effective in reducing seizure frequency, and seems to be fairly well-tolerated. However, the trials were of relatively short duration and provided no evidence for the long term. Further trials are needed to assess the long-term effects of lamotrigine, and to compare lamotrigine with other add-on drugs.

Subpial transection surgery for epilepsy.

BACKGROUND: Nearly 30% of patients with epilepsy continue to have seizures despite using several antiepileptic drugs (AEDs). Such patients are regarded as having refractory, or uncontrolled, epilepsy. While there is no universally accepted definition of uncontrolled, or medically refractory, epilepsy, for the purposes of this review we will consider seizures as drug resistant if they have failed to respond to a minimum of two AEDs. Specialists consider that early surgical intervention may prevent seizures at a younger age, which in turn may improve the intellectual and social status of children. Many types of surgery are available for treating refractory epilepsy; one such procedure is known as subpial transection. OBJECTIVES: To assess the effects of subpial transection for focal-onset seizures and generalised tonic-clonic seizures in children and adults. SEARCH METHODS: For the latest update we searched the following databases on 7 August 2018: the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid, 1946 to August 06, 2018), ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). We imposed no language restrictions. SELECTION CRITERIA: We considered all randomised and quasi-randomised parallel-group studies, whether blinded or non-blinded. DATA COLLECTION AND ANALYSIS: Two review authors (BK and SR) independently screened trials identified by the search. The same two review authors planned to independently assess the methodological quality of studies. Had we identified studies for inclusion, one review author would have extracted the data, and the other would have verified the data. MAIN RESULTS: We found no relevant studies. AUTHORS' CONCLUSIONS: We found no evidence to support or refute the use of subpial transection surgery for patients with medically refractory epilepsy. Well-designed randomised controlled trials are needed to guide clinical practice.

Yoga for epilepsy.

BACKGROUND: This is an updated version of the original Cochrane Review published in the Cochrane Library, Issue 5, 2015.Yoga may induce relaxation and stress reduction, and influence the electroencephalogram and the autonomic nervous system, thereby controlling seizures. Yoga would be an attractive therapeutic option for epilepsy if proved effective. OBJECTIVES: To assess whether people with epilepsy treated with yoga:(a) have a greater probability of becoming seizure free;(b) have a significant reduction in the frequency or duration of seizures, or both; and(c) have a better quality of life. SEARCH METHODS: For this update, we searched the Cochrane Epilepsy Group Specialized Register (3 January 2017), the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 12) in the Cochrane Library (searched 3 January 2017), MEDLINE (Ovid, 1946 to 3 January 2017), SCOPUS (1823 to 3 January 2017), ClinicalTrials.gov (searched 3 January 2017), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (searched 3 January 2017), and also registries of the Yoga Biomedical Trust and the Research Council for Complementary Medicine. In addition, we searched the references of all the identified studies. No language restrictions were imposed. SELECTION CRITERIA: The following study designs were eligible for inclusion: randomised controlled trials (RCT) of treatment of epilepsy with yoga. The studies could be double-, single- or unblinded. Eligible participants were adults with uncontrolled epilepsy comparing yoga with no treatment or different behavioural treatments. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the trials for inclusion and extracted data. The following outcomes were assessed: (a) percentage of people rendered seizure free; (b) seizure frequency and duration; (c) quality of life. Analyses were on an intention-to-treat basis. Odds ratio (OR) with 95% confidence intervals (95% Cls) were estimated for the outcomes. MAIN RESULTS: We did not identify any new studies for this update, therefore the results are unchanged.For the previous version of the review, the authors found two unblinded trials in people with refractory epilepsy. In total these two studies included 50 people (18 treated with yoga and 32 to control interventions). Antiepileptic drugs were continued in all the participants. Baseline phase lasted three months in both studies and treatment phase from five weeks to six months in the two trials. Randomisation was by roll of a die in one study and using a computerised randomisation table in the other one but neither study provided details of concealment of allocation and were rated as unclear risk of bias. Overall, the two studies were rated as low risk of bias (all participants were included in the analysis; all expected and pre-expected outcomes were reported; no other sources of bias).The overall ORs with 95% CI were as follows: (i) seizure free for six months - for yoga versus sham yoga the OR was 14.54 (95% CI 0.67 to 316.69) and for yoga versus 'no treatment' group it was 17.31 (95% CI 0.80 to 373.45); for Acceptance and Commitment Therapy (ACT) versus yoga the OR was 1.00 (95% Cl 0.16 to 6.42); (ii) reduction in seizure frequency - the mean difference between yoga versus sham yoga group was -2.10 (95% CI -3.15 to -1.05) and for yoga versus 'no treatment' group it was -1.10 (95% CI -1.80 to -0.40); (iii) more than 50% reduction in seizure frequency - for yoga versus sham yoga group, OR was 81.00 (95% CI 4.36 to 1504.46) and for the yoga versus 'no treatment' group it was 158.33 (95% CI 5.78 to 4335.63); ACT versus yoga OR was 0.78 (95% Cl 0.04 to 14.75); (iv) more than 50% reduction in seizure duration - for yoga versus sham yoga group OR was 45.00 (95% CI 2.01 to 1006.75) and for yoga versus 'no treatment' group it was 53.57 (95% CI 2.42 to 1187.26); ACT versus yoga OR was 0.67 (95% Cl 0.10 to 4.35).In addition in Panjwani 1996 the authors reported that the one-way analysis of variance revealed no statistically significant differences between the three groups. A P-Lambda test taking into account the P values between the three groups also indicated that the duration of epilepsy in the three groups was not comparable. No data were available regarding quality of life. In Lundgren 2008 the authors reported that there was no significant difference between the yoga and ACT groups in seizure-free rates, 50% or greater reduction in seizure frequency or seizure duration at one-year follow-up. The yoga group showed significant improvement in their quality of life according to the Satisfaction With Life Scale (SWLS) (P < 0.05), while the ACT group had significant improvement in the World Health Organization Quality of Life-BREF (WHOQOL-BREF) scale (P < 0.01).Overall, we assessed the quality of evidence as low; no reliable conclusions can be drawn at present regarding the efficacy of yoga as a treatment for epilepsy. AUTHORS' CONCLUSIONS: A study of 50 subjects with epilepsy from two trials reveals a possible beneficial effect in control of seizures. Results of the overall efficacy analysis show that yoga treatment was better when compared with no intervention or interventions other than yoga (postural exercises mimicking yoga). There was no difference between yoga and Acceptance and Commitment Therapy. However no reliable conclusions can be drawn regarding the efficacy of yoga as a treatment for uncontrolled epilepsy, in view of methodological deficiencies such as limited number of studies, limited number of participants randomised to yoga, lack of blinding and limited data on quality-of-life outcome. Physician blinding would normally be taken to be the person delivering the intervention, whereas we think the 'physician' would in fact be the outcome assessor (who could be blinded), so that would be a reduction in detection bias rather than performance bias. In addition, evidence to inform outcomes is limited and of low quality. Further high-quality research is needed to fully evaluate the efficacy of yoga for refractory epilepsy.Since we did not find any new studies, our conclusions remain unchanged.

Lamotrigine add-on for drug-resistant partial epilepsy.

BACKGROUND: This is an updated version of the Cochrane review published in The Cochrane Library 2010, Issue 1.Epilepsy is a common neurological disorder, affecting almost 0.5% to 1% of the population. For nearly 30% of these people, their epilepsy is refractory to currently available drugs. Pharmacological treatment remains the first choice to control epilepsy. Lamotrigine is one of the newer antiepileptic drugs and is the topic of this review. Lamotrigine in combination with other antiepileptic drugs (add-on) can reduce seizures, but with some adverse effects. The aim of this systematic review was to overview the current evidence for the efficacy and tolerability of lamotrigine when used as an adjunctive treatment for people with refractory partial epilepsy. OBJECTIVES: To determine the effects of lamotrigine on (1) seizures, (2) adverse effect profile, and (3) cognition and quality of life, compared to placebo controls, when used as an add-on treatment for people with refractory partial epilepsy. SEARCH METHODS: For the previous version of the review, the authors searched the Cochrane Epilepsy Group Specialized Register (January 2010), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 1), MEDLINE (1950 to January 2010), and reference lists of articles.For this update, we searched the Cochrane Epilepsy Group Specialized Register (28 May 2015), CENTRAL (The Cochrane Library 2015, Issue 4), MEDLINE (Ovid, 1946 to May 2015), and reference lists of articles. We also contacted the manufacturers of lamotrigine (GlaxoSmithKline). No language restrictions were imposed. SELECTION CRITERIA: Randomised placebo-controlled trials of people with drug-resistant partial epilepsy of any age, in which an adequate method of concealment of randomisation was used. The studies were double-, single- or unblinded. For cross-over studies, the first treatment period was treated as a parallel trial. Eligible participants were adults or children with drug-resistant partial epilepsy. DATA COLLECTION AND ANALYSIS: For this update, two review authors independently assessed the trials for inclusion, and extracted data. Outcomes included 50% or greater reduction in seizure frequency, treatment withdrawal (any reason), adverse effects, effects on cognition and quality of life. Primary analyses were by intention-to-treat. Sensitivity best and worse case analyses were undertaken to account for missing outcome data. Pooled Risk Ratios (RR) with 95% confidence intervals (95% Cl) were estimated for the primary outcomes of seizure frequency and treatment withdrawal. For adverse effects, pooled RRs and 99% Cls were calculated. MAIN RESULTS: We did not identify any new studies for this update, therefore, the results are unchanged.For the previous version of the review, the authors found five parallel add-on studies and eight cross-over studies in adults or children with refractory focal epilepsy, and one parallel add-on study with a responder-enriched design in infants. In total, these 14 studies included 1958 participants (38 infants, 199 children, and 1721 adults). Baseline phases ranged from 4 to 12 weeks; treatment phases from 8 to 36 weeks. Overall, eleven studies (n = 1243 participants) were rated as having a low risk of bias, and three (n = 715 participants) had un unclear risk of bias due to lack of reported information around study design. Effective blinding of studies was reported in three studies (n = 504 participants). The overall risk ratio (RR) for 50% or greater reduction in seizure frequency was 1.80 (95% CI 1.45 to 2.23; 12 RCTs) for twelve studies (n = 1322 participants, adults and children) indicating that lamotrigine was significantly more effective than placebo in reducing seizure frequency. The overall RR for treatment withdrawal (for any reason) was 1.11 (95% CI 0.90 to 1.36; 14 RCTs) for fourteen studies (n = 1958 participants). The adverse events significantly associated with lamotrigine were: ataxia, dizziness, diplopia, and nausea. The RR of these adverse effects were as follows: ataxia 3.34 (99% Cl 2.01 to 5.55; 12 RCTs; n = 1524); dizziness 2.00 (99% Cl 1.51 to 2.64;13 RCTs; n = 1767); diplopia 3.79 (99% Cl 2.15 to 6.68; 3 RCTs; n = 943); nausea 1.81 (99% Cl 1.22 to 2.68; 12 RCTs; n = 1486). The limited data available precluded any conclusions about effects on cognition and quality of life. No important heterogeneity between studies was found for any of the outcomes. Overall, we assessed the evidence as high to moderate quality, due to incomplete data for some outcomes. AUTHORS' CONCLUSIONS: Lamotrigine as an add-on treatment for partial seizures appears to be effective in reducing seizure frequency, and seems to be fairly well tolerated. However, the trials were of relatively short duration and provided no evidence for the long-term. Further trials are needed to assess the long-term effects of lamotrigine, and to compare it with other add-on drugs.Since we did not find any new studies, our conclusions remain unchanged.

Subpial transection surgery for epilepsy.

BACKGROUND: Nearly 30% of patients with epilepsy continue to have seizures in spite of using several antiepileptic drug (AED) regimens. Such patients are regarded as having refractory, or uncontrolled, epilepsy. No definition of uncontrolled, or medically refractory, epilepsy has been universally accepted, but for the purposes of this review, we will consider seizures as drug resistant if they have failed to respond to a minimum of two AEDs. It is believed that early surgical intervention may prevent seizures at a younger age, which, in turn, may improve the intellectual and social status of children. Many types of surgery are available for treatment of refractory epilepsy; one such procedure is known as subpial transection. OBJECTIVES: To determine the benefits and adverse effects of subpial transection for partial-onset seizures and generalised tonic-clonic seizures in children and adults. SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialised Register (29 June 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; May 2015, Issue 5) and MEDLINE (1946 to 29 June 2015). We imposed no language restrictions. SELECTION CRITERIA: We considered all randomised and quasi-randomised parallel-group studies, whether blinded or non-blinded. DATA COLLECTION AND ANALYSIS: Two review authors (BK and SR) independently screened trials identified by the search. The same two review authors planned to independently assess the methodological quality of studies. When studies were identified for inclusion, one review author would have extracted the data, and the other would have verified the data. MAIN RESULTS: We found no relevant studies. AUTHORS' CONCLUSIONS: We found no evidence to support or refute use of subpial transection surgery for patients with medically refractory epilepsy. Well-designed randomised controlled trials are needed to guide clinical practice.

Yoga for epilepsy.

BACKGROUND: This is an updated version of the original Cochrane review published in The Cochrane Library, Issue 1, 2002.Yoga may induce relaxation and stress reduction, and influence the electroencephalogram and the autonomic nervous system, thereby controlling seizures. Yoga would be an attractive therapeutic option for epilepsy if proved effective. OBJECTIVES: To assess whether people with epilepsy treated with yoga:(a) have a greater probability of becoming seizure free;(b) have a significant reduction in the frequency or duration of seizures, or both; and(c) have a better quality of life. SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialized Register (26 March 2015), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 26 March 2015), MEDLINE (Ovid, 1946 to 26 March 2015), SCOPUS (1823 to 9 January 2014), ClinicalTrials.gov (26 March 2015), the World Health Organization (WHO) International Clinical Trials Registry Platform ICTRP (26 March 2015), and also registries of the Yoga Biomedical Trust and the Research Council for Complementary Medicine. In addition, we searched the references of all the identified studies. No language restrictions were imposed. SELECTION CRITERIA: The following study designs were eligible for inclusion: randomised controlled trials (RCT) of treatment of epilepsy with yoga. Eligible participants were adults with uncontrolled epilepsy comparing yoga with no treatment or different behavioural treatments. DATA COLLECTION AND ANALYSIS: Three review authors independently selected trials for inclusion and extracted data. The following outcomes were assessed: (a) percentage of people rendered seizure free; (b) seizure frequency and duration; (c) quality of life. Analyses were on an intention-to-treat basis. Odds ratio (OR) with 95% confidence intervals (95% Cl) were estimated for the outcomes. MAIN RESULTS: Two unblinded trials recruited a total of 50 people (18 treated with yoga and 32 to control interventions). Antiepileptic drugs were continued in all the participants. Baseline phase lasted 3 months in both studies and treatment phase from 5 weeks to 6 months in the two trials. Randomisation was by roll of a die in one study and using a computerised randomisation table in the other one but neither study provided details of concealment of allocation and were rated as unclear risk of bias. Overall, the two studies were rated as low risk of bias (all participants were included in the analysis; all expected and pre-expected outcomes were reported; no other sources of bias). The overall OR with 95% confidence interval (CI) was: (i) seizure free for six months - for yoga versus sham yoga ORs of 14.54 (95% CI 0.67 to 316.69) and for yoga versus no treatment group 17.31 (95% CI 0.80 to 373.45); for Acceptance and Commitment Therapy (ACT) versus yoga ORs of 1.00 (95% Cl 0.16 to 6.42; (ii) reduction in seizure frequency - the Mean Difference between yoga versus sham yoga group was -2.10 (95% CI -3.15 to -1.05) and for yoga versus no treatment group -1.10 (95% CI -1.80 to -0.40); (iii) more than 50% reduction in seizure frequency - for yoga versus sham yoga group ORs of 81.00 (95% CI 4.36 to 1504.46) and for the yoga versus no treatment group 158.33 (95% CI 5.78 to 4335.63); ACT versus yoga ORs of 0.78 (95% Cl 0.04 to 14.75); (iv) more than 50% reduction in seizure duration - for yoga versus sham yoga group ORs of 45.00 (95% CI 2.01 to 1006.75) and for yoga versus no treatment group 53.57 (95% CI 2.42 to 1187.26); ACT versus yoga ORs of 0.67 (95% Cl 0.10 to 4.35). In addition in Panjwani 1996 the authors reported that the one-way analysis of variance revealed no statistically significant differences between the three groups. A P-Lambda test taking into account the P values between the three groups also indicated that the duration of epilepsy in the three groups was not comparable. No data were available regarding quality of life. In Lundgren 2008 the authors reported that there was no significant difference between the yoga and ACT groups in seizure free rates, 50% or greater reduction in seizure frequency or seizure duration at one year follow-up. The yoga group showed significant improvement in their quality of life according to the Satisfaction With Life Scale (SWLS) (P < 0.05), while the ACT group had significant improvement in the World Health Organization Quality of Life-BREF (WHOQOL-BREF) scale (P < 0.01). AUTHORS' CONCLUSIONS: Study of 50 subjects with epilepsy from two trials reveals possible beneficial effect in control of seizures. Results of the overall efficacy analysis show that yoga treatment was better when compared with no intervention or interventions other than yoga (postural exercises mimicking yoga). There was no difference between yoga and Acceptance and Commitment Therapy. However no reliable conclusions can be drawn regarding the efficacy of yoga as a treatment for uncontrolled epilepsy, in view of methodological deficiencies such as limited number of studies, limited number of participants randomised to yoga, lack of blinding and limited data on quality-of-life outcome. Physician blinding would normally be taken to be the person delivering the intervention, whereas we think the 'physician' would in fact be the outcome assessor (who could be blinded), so that would be a reduction in detection bias rather than performance bias. In addition, evidence to inform outcomes is limited and of low quality. Further high-quality research is needed to fully evaluate the efficacy of yoga for refractory epilepsy.

Subpial transection surgery for epilepsy.

BACKGROUND: Nearly 30% of patients with epilepsy continue to have seizures in spite of several antiepileptic drug (AED) regimens. In such cases they are regarded as having refractory, or uncontrolled epilepsy.There is no universally accepted definition for uncontrolled or medically refractory epilepsy, but for the purpose of this review, we will consider seizures to be drug resistant if they failed to respond to a minimum of two AEDs. It is believed that early surgical intervention may prevent seizures at a younger age and improve the intellectual and social status of children. There are many types of surgery for refractory epilepsy with subpial transection being one. OBJECTIVES: Our main aim is to determine the benefits and adverse effects of subpial transection for partial-onset seizures and generalised tonic-clonic seizures in children and adults. SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialised Register (8 August 2013), The Cochrane Central Register of Controlled Trials (CENTRAL Issue 7 of 12, The Cochrane Library July 2013), and MEDLINE (1946 to 8 August 2013). We did not impose any language restrictions. SELECTION CRITERIA: We considered all randomised and quasi-randomised parallel group studies either blinded or non-blinded. DATA COLLECTION AND ANALYSIS: Two review authors (BK and SR) independently screened the trials identified by the search. The same two authors planned to independently assess the methodological quality of studies. If studies had been identified for inclusion, one author would have extracted the data and the other would have verified it. MAIN RESULTS: No relevant studies were found. AUTHORS' CONCLUSIONS: There is no evidence to support or refute the use of subpial transection surgery for medically refractory cases of epilepsy. Well designed randomised controlled trials are needed in future to guide clinical practice.

Epilepsy (generalised).

INTRODUCTION: About 3% of people will be diagnosed with epilepsy during their lifetime, but about 70% of people with epilepsy eventually go into remission. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of monotherapy in newly diagnosed generalised epilepsy (tonic clonic type)? What are the effects of additional treatments in people with drug-resistant generalised epilepsy? What are the effects of surgery in people with drug-resistant generalised epilepsy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 8 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: monotherapy using carbamazepine, gabapentin, lamotrigine, levetiracetam, phenobarbital, phenytoin, sodium valproate, or topiramate; addition of second-line drugs (lamotrigine or levetiracetam) for drug-resistant epilepsy; and hemispherectomy for drug-resistant epilepsy.

Ayurvedic treatments for diabetes mellitus.

BACKGROUND: Patients with diabetes frequently use complimentary and alternative medications including Ayurvedic medications and hence it is important to determine their efficacy and safety. OBJECTIVES: To assess the effects of Ayurvedic treatments for diabetes mellitus. SEARCH METHODS: We searched The Cochrane Library (issue 10, 2011), MEDLINE (until 31 August 2011), EMBASE (until 31 August 2011), AMED (until 14 October 2011), the database of randomised trials from South Asia (until 14 October 2011), the database of the grey literature (OpenSigle, until 14 October 2011) and databases of ongoing trials (until 14 October 2011). In addition we performed hand searches of several journals and reference lists of potentially relevant trials. SELECTION CRITERIA: We included randomized trials of at least two months duration of Ayurvedic interventions for diabetes mellitus. Participants of both genders, all ages and any type of diabetes were included irrespective of duration of diabetes, antidiabetic treatment, comorbidity or diabetes related complications. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data. Risk of bias of trials was evaluated as indicated in the Cochrane Handbook for Systematic Reviews of Intervention. MAIN RESULTS: Results of only a limited number of studies could be combined, in view of different types of interventions and variable quality of data. We found six trials of proprietary herbal mixtures and one of whole system Ayurvedic treatment. These studies enrolled 354 participants ( 172 on treatment, 158 on controls, 24 allocation unknown). The treatment duration ranged from 3 to 6 months. All these studies included adults with type 2 diabetes mellitus.With regard to our primary outcomes, significant reductions in glycosylated haemoglobin A1c (HbA1c), fasting blood sugar (FBS) or both were observed with Diabecon, Inolter and Cogent DB compared to placebo or no additional treatment, while no significant hypoglycaemic response was found with Pancreas tonic and Hyponidd treatment. The study of whole system Ayurvedic treatment did not provide data on HbA1c and FBS values. One study of Pancreas tonic treatment did not detect a significant change in health-related quality of life. The main adverse effects reported were drug hypersensitivity (one study, one patient in the treatment arm); hypoglycaemic episodes (one study, one participant in the treatment arm; none had severe hypoglycaemia) and gastrointestinal side effects in one study (1 of 20 in the intervention group and 0 of 20 participants in the control group). None of the included studies reported any deaths, renal, hematological or liver toxicity.With regard to our secondary outcomes, post prandial blood sugar (PPBS) was lower among participants treated with Diabecon, was unchanged with Hyponidd and was higher in patients treated with Cogent DB. Treatment with Pancreas tonic and Hyponidd did not affect lipid profile significantly, while patients treated with Inolter had significantly higher HDL- and lower LDL-cholesterol as well as lower triglycerides. Cogent DB treated participants also had lower total cholesterol and triglycerides.Studies of treatment with Diabecon reported increased fasting insulin levels; one study of treatment with Diabecon reported higher stimulated insulin levels and fasting C-peptide levels in the treatment group. There was no significant difference in fasting and stimulated C-peptide and insulin levels with Hyponidd, Cogent DB and Pancreas tonic treatment. The study of Inolter did not assess these outcomes.No study reported on or was designed to investigate diabetic complications, death from any cause and economic data. AUTHORS' CONCLUSIONS: Although there were significant glucose-lowering effects with the use of some herbal mixtures, due to methodological deficiencies and small sample sizes we are unable to draw any definite conclusions regarding their efficacy. Though no significant adverse events were reported, there is insufficient evidence at present to recommend the use of these interventions in routine clinical practice and further studies are needed.

Epilepsy (partial).

INTRODUCTION: About 3% of people will be diagnosed with epilepsy during their lifetime, but about 70% of people with epilepsy eventually go into remission. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of starting antiepileptic drug treatment following a single seizure? What are the effects of drug monotherapy in people with partial epilepsy? What are the effects of additional drug treatments in people with drug-resistant partial epilepsy? What is the risk of relapse in people in remission when withdrawing antiepileptic drugs? What are the effects of behavioural and psychological treatments for people with epilepsy? What are the effects of surgery in people with drug-resistant temporal lobe epilepsy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 83 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: antiepileptic drugs after a single seizure; monotherapy for partial epilepsy using carbamazepine, gabapentin, lamotrigine, levetiracetam, phenobarbital, phenytoin, sodium valproate, or topiramate; addition of second-line drugs for drug-resistant partial epilepsy (allopurinol, eslicarbazepine, gabapentin, lacosamide, lamotrigine, levetiracetam, losigamone, oxcarbazepine, retigabine, tiagabine, topiramate, vigabatrin, or zonisamide); antiepileptic drug withdrawal for people with partial or generalised epilepsy who are in remission; behavioural and psychological treatments for partial or generalised epilepsy (biofeedback, cognitive behavioural therapy (CBT), educational programmes, family counselling, relaxation therapy (alone or plus behavioural modification therapy, yoga); and surgery for drug-resistant temporal lobe epilepsy ( lesionectomy, temporal lobectomy, vagus nerve stimulation as adjunctive therapy).

Anthelmintics for people with neurocysticercosis.

BACKGROUND: Neurocysticercosis is an infection of the brain by the larval stage of the pork tapeworm. In endemic areas it is a common cause of epilepsy. Anthelmintics (albendazole or praziquantel) may be given to kill the parasites. However, there are potential adverse effects, and the parasites may eventually die without treatment. OBJECTIVES: To assess the effectiveness and safety of anthelmintics for people with neurocysticercosis. SEARCH STRATEGY: In May 2009 we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2009, Issue 2), MEDLINE, EMBASE, LILACS, and the mRCT. SELECTION CRITERIA: Randomized controlled trials comparing anthelmintics with placebo, no anthelmintic, or other anthelmintic regimen for people with neurocysticercosis. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials, extracted data, and assessed each trial's risk of bias. We calculated risk ratios (RR) for dichotomous variables, with 95% confidence intervals (CI). We pooled data from trials with similar interventions and outcomes. MAIN RESULTS: For viable lesions in children, there were no trials. For viable lesions in adults, no difference was detected for albendazole compared with no treatment for recurrence of seizures (116 participants, one trial); but fewer participants with albendazole had lesions at follow up (RR 0.56, 95% CI 0.45 to 0.70; 192 participants, two trials).For non-viable lesions in children, seizures recurrence was less common with albendazole compared with no treatment (RR 0.49, 95% CI 0.32 to 0.75; 329 participants, four trials). There was no difference detected in the persistence of lesions at follow up (570 participants, six trials). For non-viable lesions in adults, there were no trials.In trials including viable, non-viable or mixed lesions (in both children and adults), headaches were more common with albendazole alone (RR 9.49, 95% CI 1.40 to 64.45; 106 participants, two trials), but no difference was detected in one trial giving albendazole with corticosteroids (116 participants, one trial). AUTHORS' CONCLUSIONS: In patients with viable lesions, evidence from trials of adults suggests albendazole may reduce the number of lesions. In trials of non-viable lesions, seizure recurrence was substantially lower with albendazole, which is counter-intuitive. It may be that steroids influence headache during treatment, but further research is needed to test this.

Anthelmintics for people with neurocysticercosis.

BACKGROUND: Neurocysticercosis is an infection of the brain by the larval stage of the pork tapeworm. In endemic areas it is a common cause of epilepsy. Anthelmintics (albendazole or praziquantel) may be given to kill the parasites. However, there are potential adverse effects, and the parasites may eventually die without treatment. OBJECTIVES: To assess the effectiveness and safety of anthelmintics for people with neurocysticercosis. SEARCH STRATEGY: In May 2009 we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2008, Issue 3), MEDLINE, EMBASE, LILACS, and the mRCT. SELECTION CRITERIA: Randomized controlled trials comparing anthelmintics with placebo, no anthelmintic, or other anthelmintic regimen for people with neurocysticercosis. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials, extracted data, and assessed each trial's risk of bias. We calculated risk ratios (RR) for dichotomous variables, with 95% confidence intervals (CI). We pooled data from trials with similar interventions and outcomes. MAIN RESULTS: For viable lesions in children, there were no trials. For viable lesions in adults, no difference was detected for albendazole compared with no treatment for recurrence of seizures (116 participants, one trial); but fewer participants with albendazole had lesions at follow up (RR 0.56, 95% CI 0.45 to 0.70; 192 participants, two trials).For non-viable lesions in children, seizures recurrence was less common with albendazole compared with no treatment (RR 0.49, 95% CI 0.32 to 0.75; 329 participants, four trials). There was no difference detected in the persistence of lesions at follow up (570 participants, six trials). For non-viable lesions in adults, there were no trials.In trials including viable, non-viable or mixed lesions (in both children and adults), headaches were more common with albendazole alone (RR 9.49, 95% CI 1.40 to 64.45; 106 participants, two trials), but no difference was detected in one trial giving albendazole with corticosteroids (116 participants, one trial). AUTHORS' CONCLUSIONS: In patients with viable lesions, evidence from trials of adults suggests albendazole may reduce the number of lesions. In trials of non-viable lesions, seizure recurrence was substantially lower with albendazole, which is counter-intuitive. It may be that steroids influence headache during treatment, but further research is needed to test this.

Guidelines for epilepsy management in India classification of seizures and epilepsy syndromes.

This article is part of the Guidelines for Epilepsy management in India. This article reviews the classification systems used for epileptic seizures and epilepsy and present the recommendations based on current evidence. At present, epilepsy is classified according to seizure type and epilepsy syndrome using the universally accepted International League Against Epilepsy (ILAE) classification of epileptic seizures and epilepsy syndromes. A multi-axial classification system incorporating ictal phenomenology, seizure type, epilepsy syndrome, etiology and impairments is being developed by the ILAE task force. The need to consider age-related epilepsy syndromes is particularly important in children with epilepsy. The correct classification of seizure type and epilepsy syndrome helps the individual with epilepsy to receive appropriate investigations, treatment, and information about the likely prognosis.

Epilepsy (partial).

INTRODUCTION: About 3% of people will be diagnosed with epilepsy during their lifetime, but about 70% of people with epilepsy eventually go into remission. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of starting antiepileptic drug treatment following a single seizure? What are the effects of drug monotherapy in people with partial epilepsy? What are the effects of additional drug treatments in people with drug-resistant partial epilepsy? What is the risk of relapse in people in remission when withdrawing antiepileptic drugs? What are the effects of behavioural and psychological treatments for people with epilepsy? What are the effects of surgery in people with drug-resistant temporal lobe epilepsy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 83 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: antiepileptic drugs after a single seizure; monotherapy for partial epilepsy using carbamazepine, gabapentin, lamotrigine, levetiracetam, phenobarbital, phenytoin, sodium valproate, or topiramate; addition of second-line drugs for drug-resistant partial epilepsy (allopurinol, eslicarbazepine, gabapentin, lacosamide, lamotrigine, levetiracetam, losigamone, oxcarbazepine, retigabine, tiagabine, topiramate, vigabatrin, or zonisamide); antiepileptic drug withdrawal for people with partial or generalised epilepsy who are in remission; behavioural and psychological treatments for partial or generalised epilepsy (biofeedback, cognitive behavioural therapy (CBT), educational programmes, family counselling, relaxation therapy (alone or plus behavioural modification therapy, yoga); and surgery for drug-resistant temporal lobe epilepsy ( lesionectomy, temporal lobectomy, vagus nerve stimulation as adjunctive therapy).

Epilepsy (generalised).

INTRODUCTION: About 3% of people will be diagnosed with epilepsy during their lifetime, but about 70% of people with epilepsy eventually go into remission. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of monotherapy in newly diagnosed generalised epilepsy (tonic clonic type)? What are the effects of additional treatments in people with drug-resistant generalised epilepsy? What are the effects of surgery in people with drug-resistant generalised epilepsy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found eight systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: monotherapy using carbamazepine, gabapentin, lamotrigine, levetiracetam, phenobarbital, phenytoin, sodium valproate, or topiramate; addition of second-line drugs (lamotrigine or levetiracetam) for drug-resistant epilepsy; and hemispherectomy for drug-resistant epilepsy.

Epilepsy.

INTRODUCTION: About 3% of people will be diagnosed with epilepsy during their lifetime, but about 70% of people with epilepsy eventually go into remission. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the benefits and risks of starting anti-epileptic drug treatment following a single seizure? What are the effects of monotherapy in newly diagnosed partial epilepsy, and in newly diagnosed generalised epilepsy (tonic clonic type)? What are the effects of additional treatments in people with drug-resistant partial epilepsy? Which people in remission from seizures are at risk of relapse on withdrawal of drug treatment? What are the effects of behavioural and psychological treatments for people with epilepsy? What are the effects of surgery in people with drug-resistant temporal lobe epilepsy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 59 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: addition of second-line drugs (gabapentin, levetiracetam, lamotrigine, oxcarbazepine, tiagabine, topiramate, vigabatrin, or zonisamide), amygdalohippocampectomy, anti-epileptic drug withdrawal for people in remission, anti-epileptic drugs after a single seizure, biofeedback, carbamazepine, cognitive behavioural therapy (CBT), educational programmes, family counselling, hemispherectomy, lesionectomy, phenobarbital, phenytoin, relaxation therapy (alone or plus behavioural modification therapy), sodium valproate, temporal lobectomy, topiramate, vagus nerve stimulation as adjunctive therapy for partial seizures, and yoga.

Once-daily extended-release levetiracetam as adjunctive treatment of partial-onset seizures in patients with epilepsy: a double-blind, randomized, placebo-controlled trial.

PURPOSE: Double-blind randomized trial to assess efficacy and tolerability of once-daily extended-release levetiracetam (LEV XR) tablets (2 x 500 mg) as add-on therapy in patients (12-70 years old) with partial-onset seizures (POS) refractory to one to three antiepileptic drugs. METHODS: After an 8-week prospective baseline-period, eligible patients were randomized (1:1) to once-daily LEV XR 1,000 mg/day or placebo for 12 weeks. Evaluations included changes from baseline in POS-frequency/week, responders (>or=50% reduction in POS-frequency/week), seizure-freedom, adverse events, laboratory tests, physical and neurologic examinations, vital signs, body-weight, and 12-lead electrocardiogram. RESULTS: Of 188 patients screened, 158 were randomized (intention-to-treat population): LEV XR (n = 79) or placebo (n = 79). Seventy-one (89.9%) LEV XR and 72 (91.1%) placebo patients completed the trial. Median POS-frequency/week reduction was 46.1% on LEV XR and 33.4% on placebo. Estimated reduction with LEV XR over placebo was 14.4% (p = 0.038). Thirty-four (43%) LEV XR and 23 (29.1%) placebo patients experienced >or=50% reduction in POS-frequency/week. Eight (10.1%) patients receiving LEV XR and one (1.3%) receiving placebo were free of POS during the 12-week treatment period. Forty-one (53.2%) LEV XR and 43 (54.4%) placebo patients reported >or=1 adverse event. Adverse events reported with an incidence >5% and seen more often with LEV XR than with placebo were somnolence, influenza, irritability, nasopharyngitis, dizziness, and nausea. DISCUSSION: Once-daily LEV XR 1,000 mg was effective and well-tolerated as adjunct therapy in patients with POS. Ten percent of patients randomized to LEV XR experienced freedom from POS. These results support the clinical value of this new LEV XR formulation.

Psychological treatments for epilepsy.

BACKGROUND: Psychological interventions such as relaxation therapy, cognitive behaviour therapy, bio-feedback and educational interventions have been used alone or in combination in the treatment of epilepsy, to reduce the seizure frequency and improve the quality of life. OBJECTIVES: To assess whether the treatment of epilepsy with psychological methods is effective in reducing seizure frequency and/or leads to a better quality of life. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group's Specialized Register (1 July 2007), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2007), and MEDLINE (1966 to March 2007). No language restrictions were imposed. We checked the reference lists of retrieved studies for additional reports of relevant studies. SELECTION CRITERIA: Randomized or quasi-randomized studies assessing one or more types of psychological or behaviour modification techniques for people with epilepsy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the trials for inclusion and extracted data. Primary analyses were by intention to treat. Outcomes included reduction in seizure frequency and quality of life. MAIN RESULTS: We found three small trials (50 participants) of relaxation therapy. They were of poor methodological quality and a meta-analysis was therefore not undertaken. No study found a significant effect of relaxation therapy on seizure frequency. Two trials found cognitive behavioural therapy (CBT) to be effective in reducing depression, among people with epilepsy with a depressed affect, whilst another did not. Two trials of CBT found improvement in quality of life scores. One trial of group cognitive therapy found no significant effect on seizure frequency while another trial found statistically significant reduction in seizure frequency as well as in seizure index (product of seizure frequency and seizure duration in seconds) among subjects treated with CBT. Two trials of combined relaxation and behaviour therapy and one of EEG bio-feedback and four of educational interventions did not provide sufficient information to assess their effect on seizure frequency. One small study of galvanic skin response biofeedback reported significant reduction in seizure frequency. Combined use of relaxation and behaviour modification was found beneficial for anxiety and adjustment in one study. In one study EEG bio-feedback was found to improve the cognitive and motor functions in individuals with greatest seizure reduction. Educational interventions were found to be beneficial in improving the knowledge and understanding of epilepsy, coping with epilepsy, compliance to medication and social competencies. AUTHORS' CONCLUSIONS: In view of methodological deficiencies and limited number of individuals studied, we have found no reliable evidence to support the use of these treatments and further trials are needed.